Abstract
Leptin, the ob gene product, is an adipocyte-secreted hormone that centrally regulates weight by decreasing caloric intake and increasing energy expenditure. Expression of leptin is regulated by dietary status, insulin, glucocorticoids and catecholamines. Pancreastatin (PST), a chromogranin A-derived peptide, correlates with catecholamine levels, and may play a role in the physiology of stress, modulating endocrine secretion and metabolism. Thus, PST has been found to exert a lipolytic and anti-insulin effect in white adipocytes. The aim of the present work was to investigate a possible role of PST modulating the expression of key genes involved in lipid storage and metabolism: leptin, PPAR-γ2, UCP-1 and UCP-2. We incubated isolated rat epididymal adipocytes with 100 nM PST for 16 and 24 h. Leptin, UCP-2 and UCP-1 mRNA levels were assessed by RT-PCR, followed by Southern blot. Leptin secretion was also measured by ELISA. PST inhibited leptin expression and secretion at 16-h incubation, but this effect was no longer observed after 24 h. On the other hand, PST stimulated the expression of UCP-2 after 16 h. However, the effect was still significant after 24 h. The inhibitory effect of PST on leptin expression and secretion and the stimulation of UCP-2 expression were prevented by blocking PKC. UCP-1 and PPR-γ2 expression did not change after PST stimulation. Leptin differentially regulates the expression of key genes in the rat adipocyte, upregulating the expression of UCP-2 and inhibiting the expression and secretion of leptin by a mechanism that involves PKC activity. These effects may contribute to the metabolic action of catecholamines in physiological and pathophysiological conditions with increased sympathetic activity.
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Received 5 September 2003; received after revision 6 October 2003; accepted 14 October 2003
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González-Yanes, C., Sánchez-Margalet, V. Pancreastatin, a chromogranin A-derived peptide, inhibits leptin and enhances UCP-2 expression in isolated rat adipocytes. CMLS, Cell. Mol. Life Sci. 60, 2749–2756 (2003). https://doi.org/10.1007/s00018-003-3346-7
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DOI: https://doi.org/10.1007/s00018-003-3346-7